Brain tumors have claimed the lives of 13,300 people in 1995. The number of deaths caused by brain tumors are increasing each year. Over 17,900 will die in 1996. Brain tumors claim lives of not only adults but also of children. The increased incidence of brain tumors is not only evident in the young but also in adults. It has been documented that a significant increase in mortality has occurred in adult primary malignant brain tumors between 1982 and 1996 (Parker et al., 1996, CA Cancer J. Clin. 46:5-28).
Glioblastomas, astrocytomas and meningiomas are the most common brain tumors that affect adults. Glioblastoma multiforme are high grade astrocytomas that grow very rapidly and contain cells that are malignant (Laws and Thapar, 1993, CA Cancer J. Clin. 43:262-271). The molecular basis of glioblastoma multiforme may involve systematic events at the chromosomal level or at the gene expression level. These may include inactivation of tumor suppressor genes, activation of oncogenes or specific translocations at the chromosomal level. Genetic changes at the chromosomal level and gene expression level are well documented for other brain tumors (Furnari et al., 1995. Cancer Surveys 25:223-275).
Tumor suppressor genes play an important role in normal cell growth, differentiation and progression through the cell cycle. Tumor suppressor genes in humans have been identified through studies of genetic changes occurring in cancer cells (Ponder, 1990, Trends Genet. 6:213-218; Weinberg, 1991, Science 254:1138-1146). Mutations that cause change in gene expression of tumor suppressor genes lead to cell transformation in vitro and tumor development in vivo. It has been documented that loss of tumor suppressor(s) genes at chromosome 10, mutations in p53 or overexpression of epidermal growth factor receptor may be major events leading to glioblastoma multiforme (Furnari et al., 1995, Cancer Surveys 25:223-271; Bogler et al., 1995, GLIA 15:308-327; Faillot et al., 1996, Neurosurgery 39:478-483). The exact series of events involving tumor suppressor genes that lead to initiation and progression of glioblastoma is not known.
Citation of references in this section or any section of this application shall not be construed as an admission that such references are available as prior art to the present invention.